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Human induced pluripotent stem cells improve recovery in stroke-injured aged rats.

Tatarishvili, Jemal LU ; Oki, Koichi LU ; Monni, Emanuela LU ; Koch, Philipp; Memanishvili, Tamar LU ; Buga, Ana-Maria; Verma, Vivek LU ; Popa-Wagner, Aurel; Brüstle, Oliver and Lindvall, Olle LU , et al. (2014) In Restorative Neurology and Neuroscience 32(4). p.547-558
Abstract
Purpose: Induced pluripotent stem cells (iPSCs) improve behavior and form neurons after implantation into the stroke-injured adult rodent brain. How the aged brain responds to grafted iPSCs is unknown. We determined survival and differentiation of grafted human fibroblast-derived iPSCs and their ability to improve recovery in aged rats after stroke. Methods: Twenty-four months old rats were subjected to 30 min distal middle cerebral artery occlusion causing neocortical damage. After 48 h, animals were transplanted intracortically with human iPSC-derived long-term neuroepithelial-like stem (hiPSC-lt-NES) cells. Controls were subjected to stroke and were vehicle-injected. Results: Cell-grafted animals performed better than vehicle-injected... (More)
Purpose: Induced pluripotent stem cells (iPSCs) improve behavior and form neurons after implantation into the stroke-injured adult rodent brain. How the aged brain responds to grafted iPSCs is unknown. We determined survival and differentiation of grafted human fibroblast-derived iPSCs and their ability to improve recovery in aged rats after stroke. Methods: Twenty-four months old rats were subjected to 30 min distal middle cerebral artery occlusion causing neocortical damage. After 48 h, animals were transplanted intracortically with human iPSC-derived long-term neuroepithelial-like stem (hiPSC-lt-NES) cells. Controls were subjected to stroke and were vehicle-injected. Results: Cell-grafted animals performed better than vehicle-injected recipients in cylinder test at 4 and 7 weeks. At 8 weeks, cell proliferation was low (0.7 %) and number of hiPSC-lt-NES cells corresponded to 49.2% of that of implanted cells. Transplanted cells expressed markers of neuroblasts and mature and GABAergic neurons. Cell-grafted rats exhibited less activated microglia/macrophages in injured cortex and neuronal loss was mitigated. Conclusions: Our study provides the first evidence that grafted human iPSCs survive, differentiate to neurons and ameliorate functional deficits in stroke-injured aged brain. (Less)
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publication status
published
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Restorative Neurology and Neuroscience
volume
32
issue
4
pages
547 - 558
publisher
IOS Press
external identifiers
  • pmid:24916776
  • wos:000340031000009
  • scopus:84908294733
ISSN
1878-3627
DOI
10.3233/RNN-140404
language
English
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yes
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80061e04-0011-4ba5-b0dd-ad7b713314f3 (old id 4528889)
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http://www.ncbi.nlm.nih.gov/pubmed/24916776?dopt=Abstract
date added to LUP
2014-07-05 17:14:44
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2017-10-01 03:16:20
@article{80061e04-0011-4ba5-b0dd-ad7b713314f3,
  abstract     = {Purpose: Induced pluripotent stem cells (iPSCs) improve behavior and form neurons after implantation into the stroke-injured adult rodent brain. How the aged brain responds to grafted iPSCs is unknown. We determined survival and differentiation of grafted human fibroblast-derived iPSCs and their ability to improve recovery in aged rats after stroke. Methods: Twenty-four months old rats were subjected to 30 min distal middle cerebral artery occlusion causing neocortical damage. After 48 h, animals were transplanted intracortically with human iPSC-derived long-term neuroepithelial-like stem (hiPSC-lt-NES) cells. Controls were subjected to stroke and were vehicle-injected. Results: Cell-grafted animals performed better than vehicle-injected recipients in cylinder test at 4 and 7 weeks. At 8 weeks, cell proliferation was low (0.7 %) and number of hiPSC-lt-NES cells corresponded to 49.2% of that of implanted cells. Transplanted cells expressed markers of neuroblasts and mature and GABAergic neurons. Cell-grafted rats exhibited less activated microglia/macrophages in injured cortex and neuronal loss was mitigated. Conclusions: Our study provides the first evidence that grafted human iPSCs survive, differentiate to neurons and ameliorate functional deficits in stroke-injured aged brain.},
  author       = {Tatarishvili, Jemal and Oki, Koichi and Monni, Emanuela and Koch, Philipp and Memanishvili, Tamar and Buga, Ana-Maria and Verma, Vivek and Popa-Wagner, Aurel and Brüstle, Oliver and Lindvall, Olle and Kokaia, Zaal},
  issn         = {1878-3627},
  language     = {eng},
  number       = {4},
  pages        = {547--558},
  publisher    = {IOS Press},
  series       = {Restorative Neurology and Neuroscience},
  title        = {Human induced pluripotent stem cells improve recovery in stroke-injured aged rats.},
  url          = {http://dx.doi.org/10.3233/RNN-140404},
  volume       = {32},
  year         = {2014},
}